Velu T, Ravelingien N, Parma J, Pector J C
Centre de Génétique, Hôpital Erasme, Université Libre de Bruxelles.
Rev Prat. 1994 Dec 15;44(20):2694-9.
All cancers result from the accumulation of mutations of proto-oncogenes and tumor suppressor genes. Sporadic and familial colorectal cancers result from the accumulation of the following genes, in a relatively stereotyped chronological order: the tumor suppressor gene apc whose mutations are responsible for the familial adenomatous polyposis; the proto-oncogene K-ras which is mutated in 50% of large adenomas (> 1 cm) and adenocarcinomas; the tumor suppressor gene dcc; and the tumor suppressor gene p53 whose inactivation in a factor of bad prognosis. While some of them are induced by mutagens, others result from an instability of the genome. Two types of instability are observed in both sporadic and familial colorectal cancer. The first type, which is found in 25-50% of cases, appears as cytogenetic abnormalities with aneuploidy and allelic losses. The second type of instability is induced by mutations of the hMSH2 or hMLH1 genes which code for proteins involved in the mechanism of DNA repair.
所有癌症均由原癌基因和肿瘤抑制基因的突变积累所致。散发性和家族性结直肠癌是由以下基因按相对固定的时间顺序积累而成：肿瘤抑制基因apc，其突变导致家族性腺瘤性息肉病；原癌基因K-ras，在50%的大腺瘤（>1 cm）和腺癌中发生突变；肿瘤抑制基因dcc；以及肿瘤抑制基因p53，其失活是预后不良的一个因素。虽然其中一些是由诱变剂诱导的，但其他则是由基因组不稳定导致的。在散发性和家族性结直肠癌中均观察到两种类型的不稳定。第一种类型见于25%-50%的病例，表现为细胞遗传学异常，伴有非整倍体和等位基因缺失。第二种类型的不稳定是由hMSH2或hMLH1基因的突变诱导的，这些基因编码参与DNA修复机制的蛋白质。
